According to the World Health Organization, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide (“Global Cancer Statistics, 2012”, CA Cancer). In China, there were 3.37 million cancer cases and 2.11 million cancer deaths recorded in 2011, which means every minute, 6.4 people were diagnosed with cancer and 5 people died from cancer. Lung cancer ranks the first in mortality, followed by cancers of liver, stomach, esophagus and colorectum. Liver cancer has the lowest five-year survival rate, 10.1%, and lung cancer was the next, 16.1% (“Cancer statistics in China, 2015”). The incidence rate of tumor is rising year by year.
Tumors are composed of various abnormal cells at different degrees of differentiation, and characterized by heterogeneity. Current anti-tumor therapies, including radiotherapy, chemotherapy, targeted therapy, immune-biological therapy, induction of differentiation and killing and the like, are directed to killing of tumor cells, which is however clinically demonstrated as incapable of overcoming tumor heterogeneity. Moreover, these therapies are found struggling with limited therapeutic efficacy, significant toxicity, drug resistance, high recurrence rate, and low five-year survival rate. Accordingly, there is such a long-existing need for a novel anti-tumor drug having high efficacy and low toxicity to provide a new approach of anti-tumor therapy and to improve patient survival.
The basic idea proposed herein is to transdifferentiate tumor cells directly into normal or non-oncogenic cells, instead of killing them, whereby a novel therapeutic process that can overcome tumor heterogeneity with high efficacy and low toxicity is provided.
Cell reprogramming is a process in which cells are converted from one type to another by regulating cellular signaling pathways and epigenetic modification. The term “cell reprogramming” used herein mainly refers to induction of cell reprogramming and induced cell reprogramming. Cell reprogramming includes induced reprogramming of induced pluriponent stem cells (iPSCs) and direct reprogramming of cells (transdifferentiation), which has been widely used in transformation of normal types of cells. Reprogramming of certain tumor cells into iPSCs (oncogenicity maintained) by exogenous transcription factors has also been reported. The method provided herein induces and regulates tumor cells to be reprogrammed (transdifferentiated) directly into non-oncogenic cells, which is accompanied by apoptosis of tumor cells using small molecule compositions instead of transcription factors. This has never been reported.